Soft tissue augmentation with injectable fillers is widely used for cosmetic improvements and a variety of medical applications. In cosmetic procedures, fillers are used primarily to improve aesthetic appearance including scar revision, reduction in wrinkles, restoration of lost skin volume, and elimination of concavities or depressions. Other cosmetic procedures involve injection or implant of colorants, dyes, or inks to produce externally visible pigmentation or coloration. In medical applications, biomedical fillers are used to augment soft tissue volume in the larynx (to improve phonation, and/or to reduce aspiration from incomplete glottic closure). They are used in other areas of the body to augment the function of natural biological valves, such as the upper or lower esophageal sphincter, the anal sphincter, and urethral sphincters. Other medical applications of biomedical fillers include bridging or reinforcement of bone defects or fractures, particularly in the case of non-union.
Fillers known to those skilled in the art to be used for cosmetic and medical improvements include hyaluronic acid, calcium hydroxylapatite, and poly-L-lactic acid (Vleggaar et al., Journal of drugs in dermatology, 13(4 Suppl):s40-43 (2014)). While widely used, these dermal fillers are not permanent and need reapplication at 6-9 months for hyaluronic acid, 10-14 months for calcium hydroxylapatite (Emer and Sundaram, Journal of Drugs in Dermatology, 12(12):1345-54 (2013), and about every 24 months for poly L-lactic acid fillers (Vleggaar et al., Journal of drugs in dermatology, 13(4 Suppl):s40-43 (2014); Vleggaar et al., Journal of drugs in dermatology, 13(4 Suppl):s44-51 (2014); and Mest and Humble, Dermatologic Surgery, 35(Suppl 1):350-359 (2009)).
Other fillers commonly known to those skilled in the art to improve bone defects or fractures include decellularized and processed allogenic bone pate, mineralized and processed collagen particles, synthetic tricalcium phosphate particles, and various mixtures of calcium hydroxyappetite and/or calcium sulfate (e.g. Cerament™).
For all of the above categories, many of these fillers induce an unacceptable inflammatory response making them less than ideal for cosmetic or surgical procedures (Cecchi, et al., Dermatology, 228(1):14-17 (2014)). Additionally, many of these substances also have high viscosity, making it difficult for them to pass through thin needles used in clinical applications.
Therefore, it is an object of the invention to provide compositions and methods of tissue augmentation, coloration, and/or cargo delivery that are long lasting, easy to administer and evoke limited inflammatory responses.
It is another object of the invention to provide biomedical composites having a controlled and reduced viscosity.
It is another object of the invention to provide prepackaged, ready-to-use composites for tissue augmentation, biomedical, or cosmetic applications.